It is proposed to map the distribution of several biologically active peptides in the brain, spinal cord, and pituitary gland with light and electron microscopic immunocytochemistry. The following peptides will be studied: Substance P, neurotensin, thyrotropin releasing factor, gonadotropin releasing factor, somatotropin releasing factor or somatostatin, melanotropin release inhibiting factor, alpha-melanocyte stimulating hormone, and the opioid peptides enkephalins and endorphins. The peptides will be localized in histological sections with the help of specific antibodies which in turn are demonstrated with horseradish peroxidase according to the immunoglobulin-enzyme bridge method. Thus the sensitivity and specificity of the immunochemical binding is combined with the structural resolution of light and electron microscopy. This permits precise topographical localization and mapping of the peptide-containing cells, pathways and synaptic contacts in the brain. Most of the peptides to be studied have been discovered only recently. Initial work in this and other laboratories clearly indicates their widespread distribution throughout the body, but especially in the nervous and endocrine systems. They may function as neurotransmitters, modulators of neurotransmission, regulators of hormone release from the pituitary gland, or as neurohormones released directly into the blood stream. In order to conduct meaningful physiological studies with these peptides, knowledge on their precise cellular and subcellular localization as well as topographical distribution in the central nervous system will be essential. Such knowledge will also help understand the pathogenesis of certain mental diseases.